Obeticholic Acid Monotherapy Leads to Jaundice in PBC Patient

UDCA had been inadvertently discontinued
UDCA had been inadvertently discontinued

A case published in Digestive Diseases and Sciences reports on a patient with primary biliary cholangitis (PBC) who developed severe jaundice 8 weeks after abruptly discontinuing ursodeoxycholic acid (UDCA) and simultaneously starting treatment with obeticholic acid (OCA).

The patient, a 55-year-old female with PBC, had been receiving treatment with UDCA for 2 years (1500mg/day). After a liver biopsy revealed further changes consistent with PBC, OCA 5mg daily was added to her treatment regimen. However, UDCA had been inadvertently discontinued. Eight weeks later, the patient developed clinical jaundice, and a second liver biopsy revealed cholestatic hepatitis.

The patient was taken off OCA and restarted on UDCA (900mg/day), and after 4 months of UDCA monotherapy, she was reintroduced to OCA (5mg/day, increased 1 month later to 10mg/day). The authors report that she currently remains in a state of compensated cirrhosis. 

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OCA was approved by the Food and Drug Administration in 2016 for the treatment of primary biliary cholangitis in combination with UDCA in adults with inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA.

Last year, the FDA released a safety communication following 8 deaths among 19 PBC patients who developed severe jaundice upon starting OCA; the deaths occurred in patients with decompensated liver disease who had received higher than recommended doses. In addition, OCA use had been associated with liver injury in some patients with mild liver disease who were receiving appropriate doses.

The authors of this case believe that the initiation of OCA and abrupt discontinuation of UDCA resulted in an “increase in hydrophobic bile acids and reduction in bile flow, ultimately causing cholestatic hepatitis." They also note, "...it is intriguing that cholestasis worsened despite the fact that she was placed on OCA which at least theoretically should have mitigated cholestasis by increasing bile flow."

While OCA may be approved as monotherapy for PBC, the authors believe that clinicians should make sure that patients are truly not responding to UDCA before starting treatment. "Moreover, OCA should be introduced as monotherapy only after a UDCA washout period of 3 months has passed to mirror the strategy employed in the other reported OCA trials."

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